Not applicable.
1. The Field of the Invention
The present invention is in the field of hemostatic and acid etch compositions, more particularly hemostatic compositions for use in providing hemostasis in oral tissues and etching compositions used in etching teeth.
2. The Relevant Technology
In the course of performing certain dental procedures it is often desirable to use a hemostatic composition in order to stop the bleeding of oral tissues. For example, during dental reconstruction or preparation of dental crowns it is common for dentists to cut gingival or gum tissue in order to fully expose the tooth prior to taking an impression of the tooth. In order to make an accurate impression of the tooth it is advantageous for it to be clean and dry. For this reason, a hemostatic composition may be used to reduce or eliminate bleeding so that a more accurate impression of the patient""s tooth can be taken.
In the case of invasive dental procedures, such as preparing the tooth to receive a crown or forming a deep dental preparation that is to be filled with a restorative composition, sufficient enamel and dentin may be removed so as to expose the pulp chamber. It may be desirable in some cases to apply a hemostatic composition to stop or slow bleeding of the exposed pulp.
Whereas hemostatic compositions of various types have been used successfully to stop or slow the bleeding of oral tissues during a variety of dental or oral procedures, hemostatic compositions can be very unpleasant tasting. Hemostatic compositions tend to be quite acidic (i.e., typically having a pH of about 1-2), which makes them have a profound sour or bitter flavor. It is therefore preferable to avoid contacting the patient""s tongue with the hemostatic composition during the procedure in question. Allowing the hemostatic composition to contact the person""s tongue is not only unpleasant to the patient, it may even cause the patient to flinch or experience a gag reflex, both of which can hinder the dental procedure.
A similar problem exists in the case of dental etching compositions used to etch a patient""s tooth during a dental procedure. Dental etching compositions are typically used to create a superior bonding surface in dentin, enamel or both to which a restorative composition can better adhere. However, since dental etching compositions are by nature very acidic (i.e., typically having a pH of about 0-2), they also have a profound sour or bitter flavor and cause similar problems associated with hemostatic compositions.
In view of the foregoing, it would be an advancement in the art to provide better tasting hemostatic and dental etching compositions. More particularly, it would a an important advancement in the art to provide hemostatic and dental etching compositions that were more palatable to the patient in order to reduce the tendency of such compositions to startle the patient or induce a gag reflex if such compositions happen to contact the patient""s tongue.
The present invention is directed to hemostatic compositions and dental etching compositions that contain sucralose, which is a non-nutritive sweetener. The inclusion of sucralose adds a pleasant taste that at least partially offsets the otherwise sour or bitter taste of the acidic hemostatic and/or acidic dental etching agents. This, in turn, reduces the chance that a patient will be surprised or startled in the event the hemostatic composition or dental etching composition were to contact the patient""s tongue. Thus, an advantage of including sucralose within such compositions is that it creates a more pleasant experience for the patient. It may also reduce the tendency of the patient to flinch or gag if the otherwise sour or bitter composition were to contact the patient""s tongue.
One advantage of sucralose is that it is many times sweeter than sugar, which greatly reduces the amount of sweetener that must be added to offset the sour or bitter taste of the hemostatic or dental etching agent. This results in less residue that must otherwise be removed from the patient""s tooth. Another advantage of using sucralose over certain sweeteners (e.g., aspartame) is that sucralose has been found by the inventors to be stable in the presence of hemostatic or dental etching agents, both of which are highly acidic in water. Thus, sucralose is effective in disguising the sour or bitter taste of such agents even after being mixed and stored with such agents over time (e.g., weeks, months or even years). Sucralose has also been found by the inventors to leave no bitter or unpleasant after taste, which is an advantage over certain non-nutritive sweeteners, such as sodium saccharine.
The sucralose and hemostatic or dental etching agent are mixed together within an appropriate carrier, such as an aqueous liquid or gel. Water is typically used as part of the carrier in order to dissolve the sucralose, hemostatic agent and/or dental etching agent within the carrier. In the case where a sticky or viscous composition is desired, one or more thickening or tackifying agents may be included, examples of which include finely divided gel-forming metal oxides (e.g., fumed silica, precipitated or fumed aluminum oxide), organic thickeners (e.g., pemulen), or other gelling agents known in the art.
The inventive compositions may also include other adjuvents and active ingredients such as flavorants, desensitizing agents (e.g., KNO3), anticariogenic agents (e.g., fluoride compounds), antimicrobial agents (e.g., antibiotics), stabilizing agents (e.g., EDTA), and the like. The carrier is preferably substantially free of abrasives.
Depending on the desired treatment regimen, the hemostatic or dental etching compositions according to the invention may vary as desired in potency, fluidity or stickiness in order to optimize the performance of the composition for a given treatment regimen.
Examples of hemostatic agents that may be used within the inventive hemostatic compositions include, but are not limited to, ferric sulfate, ferric subsulfate, ferric chloride, zinc chloride, aluminum chloride, aluminum sulfate, aluminum chlorohydrate, aluminum acetate, alum, salts of manganese, salts of bismuth, permanganates, and tannin.
Examples of dental etching agents include, but are not limited to, mineral acids, such as phosphoric acid, nitric acid, hydrochloric acid and sulfuric acid, and organic acids, such as glycolic acid, malic acid, maleic acid, acetic acid, citric acid, and EDTA.
Hemostatic compositions according to the invention will typically have a pH of less than about 3, preferably less than about 2.5, more preferably a pH less than about 2, and most preferably a pH in a range of about 1-2. Dental etching compositions according to the invention will preferably have a pH of less than about 2, more preferably a pH less than about 1, and most preferably a pH in a range of about 0-1.
These and other features of the present invention will become more fully apparent from the following description and appended claims, or may be learned by the practice of the invention as set forth hereinafter.
As summarized above, the invention is generally related to acidic hemostatic compositions and dental etching compositions that contain sucralose, a chlorinated sucrose derivative that has greatly enhanced sweetness compared to sucrose. The purpose of the sucralose is to mask or disguise the extremely sour or bitter taste associated with hemostatic agents and/or dental etching agents.
Hemostatic compositions within the scope of the invention encompass virtually any hemostatic composition suitable for providing hemostasis in oral tissues so long as it contains sucralose. Likewise, dental etching compositions within the scope of the invention encompass virtually any dental etching composition suitable for etching teeth so long as it contains sucralose. The inventive compositions generally comprise at least one of a hemostatic agent or dental etching agent dispersed in an aqueous carrier. The carrier may be a liquid or gel and have any desired viscosity.
Examples of hemostatic compositions that have the consistency of a low viscosity liquid or fluid are ASTRINGEDENT, ASTRINGEDENT X, and BUFFERED ALUMINUM CHLORIDE, which are sold by Ultradent Products, Inc. which is located in South Jordan, Utah. Examples of more viscous hemostatic compositions are VISCOSTAT and VISCOSTAT PLUS, which are also available from Ultradent Products, Inc. ASTRINGEDENT, ASTRINGEDENT X, BUFFERED ALUMINUM CHLORIDE, VISCOSTAT, and VISCOSTAT PLUS can be modified according to the teachings disclosed herein to include sucralose in order to improve their taste.
Additional examples of hemostatic compositions that may be modified according to the present invention are set forth in U.S. Pat. No. 4,551,100 to Fischer, U.S. Pat. No. 5,635,162 to Fischer, and U.S. Pat. No. 5,785,955 to Fischer. For purposes of generally disclosing hemostatic compositions, the foregoing patents are incorporated herein by reference.
Examples of dental etching compositions that may be modified according to the invention so as to include sucralose include ULTRA-ETCH and ULTRA-ETCH AB, both of which are available from Ultradent Products, Inc.
The term xe2x80x9caboutxe2x80x9d when used in combination with a numeric value shall meanxc2x110% of the numeric value. Thus, the effect of the term xe2x80x9caboutxe2x80x9d is to define a range that is xc2x110% of the given numeric value.
The acidic dental compositions according to the invention include sucralose, at least one acidic agent such as a hemostatic agent and/or a dental etching agent, and an aqueous carrier into which the sucralose and acidic agent are dispersed. The compositions may include other ingredients as needed to yield a composition having desired properties. The acidic dental compositions are preferably formulated so as to be safe for introduction into the oral cavity of a patient.
A. Sucralose
More proper chemical names for xe2x80x9csucralosexe2x80x9d include: 1,6-dichloro-1,6-dideoxy-xcex2-D-fructo-furanosyl-4-chloro-4-deoxy-xcex1-D-galactopyranoside; 4,1xe2x80x2,6xe2x80x2-trichloro-4,1xe2x80x2,6xe2x80x2-trideoxy-galacto-sucrose; 1xe2x80x2,4,6xe2x80x2-trichloro-galactosucrose; and TGS. Sucralose has the general formula C12H19C13O8 and a molecular weight of 397.64. Publications which disclose methods for preparing sucralose include European Patent Application 0 030 804 to Tate et al. and U.S. Pat. No. 4,343,934 to Jenner et al. U.S. Pat. No. 4,435,440 to Hough et al. describes the usefulness of sucralose as a sweetener. The foregoing references are incorporated herein by reference.
Sucralose is non-nutritive so it has none of the disadvantages associated with nutritive sweeteners, e.g., promoting tooth decay. However, it tastes very much like sugar while being approximately 600 times sweeter than sugar. Because sucralose is so sweet tasting, even a small amount of sucralose is sufficient to disguise the bitter taste of the bleaching agent. Additionally, sucralose has been found to be surprisingly stable for extended periods of time when mixed with a bleaching agent. Sucralose, unlike sodium saccharine, does not itself leave a bitter after taste. Nor is it suspected of being a carcinogen. Hence, the inventive bleaching compositions of the present invention are better tasting, with stable taste properties over time, compared to compositions that use, e.g., aspartame, and safer to use, compared to compositions that use, e.g., sodium saccharine.
In order to impart a desired sweetening effect to the acidic compositions in order to disguise or mask the sour or bitter taste of the acidic agent(s) contained therein (e.g., hemostatic and/or dental etching agents), the inventive compositions according to the invention may contain any suitable quantity of sucralose. The amount of sucralose may vary depending on the desired sweetening effect and the concentration of the acidic agents contained in the acidic composition. As the concentration of the acidic agent is increased, a larger concentration of sucralose will typically be used to offset the increased level of sourness or bitterness imparted by the acidic agent(s) to the composition.
In general, the acidic compositions according to the invention will preferably contain sucralose in an amount in a range of about 0.01% to about 15% by weight of the composition, more preferably in a range of about 0.05% to about 10% by weight of the composition, and most preferably in a range of about 0.1% to about 5% by weight of the composition. The foregoing concentrations take into consideration the fact that sucralose is typically commercially available as an aqueous solution, the water forming part of the carrier once the aqueous sucralose solution has been added to a composition according to the invention.
The stability of the sucralose within the acidic compositions according to the invention is generally sufficient such that the acidic compositions can be stored for long periods of time and used as desired, while maintaining sufficient sweetness of the sucralose so as to mask the generally sour or bitter taste of the hemostatic and/or dental etching agent. For example, an acidic composition containing sucralose which is formed in accordance with the invention is likely after 1 year to still have substantially the same concentration of sucralose as it contained when originally manufactured. In any event, the sucralose content would be expected after 1 year to be at least 85% of the amount contained in the composition when initially manufactured. Similarly, the sucralose content would be expected after about 4 to 6 months to be at least 90% of the amount contained in the composition when originally manufactured.
In any event, the ultimate shelf life of a particular composition according to the invention is not limited by the stability of the sucralose within the composition. It is certainly the case that even if the sucralose loses a significant or even a substantial portion of its sweetening ability over time, the compositions will still function as intended even though they may be more sour or bitter.
B. Hemostatic Agents
Hemostatic agents for use in the inventive compositions can be selected from a wide variety of hemostatic compounds or agents known in the art, which can be used singly or in a variety of different combinations. Examples include, but are not limited to, metal salts, such as the salts of aluminum, iron, zinc, manganese, and bismuth, as well as ions that contain one or more of these metals (e.g., permanganates).
Non-limiting examples of suitable hemostatic agents that may be used within hemostatic compositions within the scope of the invention include ferric sulfate, ferric subsulfate, ferric chloride, other iron (III) salts, zinc chloride, aluminum chloride, aluminum sulfate, aluminum chlorohydrate, aluminum acetate, alums (e.g., aluminum potassium sulfate and aluminum ammonium sulfate), tannins, and polyphenolic compounds.
A currently preferred hemostatic agent for use in formulating hemostatic compositions according to the invention is a ferric salt compound. Preferred ferric salts include ferric sulfate, which has the formula Fe2(SO4)3, and ferric subsulfate, which has the formula Fe4(OH)2(SO4)5. Both ferric and sulfate ions are present within the human body. Thus, the probability of allergic reactions to ferric sulfate or ferric subsulfate is low. The ferric salts are coagulative hemostats, and when contacted with blood, the ferric salts cause an instant precipitation of blood proteins, which forms a coagulum.
The hemostatic agent may also facilitate tissue retraction by reducing the elasticity of collagen fibers within the gingival cuff. This can be beneficial in some cases as it can prevent premature closure of the sulcular space during impression placement and solidification. In addition, the hemostatic agent facilitates reduced sulcular fluid movement through intact epithelium, whether for impression making or during bonding or luting stages of the final restoration placement procedure. Finally, the hemostatic agent can be useful in stopping the bleeding of wounds in soft tissues in general.
When the acidic compositions according to the invention contain a hemostatic agent, the hemostatic agent is included in an effective amount so as to provide hemostatic properties to the composition. The hemostatic agent is preferably included within the hemostatic composition in an amount in a range of about 1% to about 40% by weight of the hemostatic composition, more preferably in a range of about 5% to about 35% by weight, and most preferably in a range of about 10% to about 30% by weight of the hemostatic composition.
Hemostatic compositions according to the invention will typically have a pH of less than about 3, preferably less than about 2.5, more preferably less than about 2, and most preferably have a pH in a range of about 1 to about 2.
C. Dental Etching Agents
Dental etching agents for use in the inventive compositions can be selected from a wide variety of acidic compounds that are capable of etching. Examples of dental etching agents include, but are not limited to, mineral acids, such as phosphoric acid, nitric acid, hydrochloric acid and sulfuric acid, and organic acids, such as glycolic acid, malic acid, maleic acid, acetic acid, citric acid, and EDTA.
When the acidic compositions according to the invention contain a dental etching agent, the etching agent is included in an effective amount so as to etch at least one of dentin or enamel. The etching agent is preferably included within the dental etching composition in an amount in a range of about 10% to about 60% by weight of the etching composition, more preferably in a range of about 20% to about 50% by weight, and most preferably in a range of about 25% to about 45% by weight of the etching composition.
Dental etching compositions within the scope of the invention will preferably have a pH of less than about 2, more preferably less than about 1, and most preferably have a pH in a range of 0 to about 1.
D. Carrier
The compositions according to the invention typically include an aqueous carrier. The water can be present as part of the other components of the composition or it can be added separately. The water may be deionized if desired prior to use in the composition. In general, water is included in an amount in a range from about 1% to about 80% by weight of the acidic composition, more preferably in a range of about 40% to about 60% by weight.
The various components may be mixed together in the desired amounts using standard mixing procedures to form the composition of the invention. If a solid hemostatic agent, such as a solid ferric salt, is used in formulating the compositions according to the invention, it is preferably to first dissolve the solid hemostatic agent in water before adding the other components of the composition.
The various polyols can be added to the compositions according to the invention. Examples of suitable polyols include polyethylene glycol, glycerin, propylene glycol, dipropylene glycol, polypropylene glycol, sorbitol, and the like. Polyols used can have a wide variety of molecular weights, with higher molecular weight polyols generally increasing the viscosity of the acidic compositions according to the invention. For example, polyols having an average molecular weight (number average) of at least about 600 may be included in order to increase the viscosity of the resulting composition. It should be understood that polyols having an average molecular weight of up to 100,000 or more may also be used. In some cases it may be desirable to mix two or more different polyols together having different molecular weights in order to yield a composition having the desired properties. When a polyol is included within the composition according to the invention, they are preferably included in an amount in a range from about 0.1% to about 50% by weight of the composition, and more preferably in a range of about 5% to about 40% by weight.
It is within the scope of the invention to include one or more thickening agents within the compositions according to the invention in order to yield a composition having the desired viscosity and/or thixotropic nature. Higher molecular weight polyols are examples of thickening agents that may be used in accordance with the invention. One organic polymer thickening agent that is relatively stable in the presence of weakly acidic compositions is PEMULEN. Other polymeric thickening agents may be used with the caveat that many thickening agents tend to break down and are unstable in the presence of strong acids.
Accordingly, it may be desirable to instead include inorganic fillers, preferably finely divided organic particulate fillers that are able to impart a thickening effect. Examples of inorganic fillers that may be used to impart a thickening effect include silica-based particulates such as colloidal silica, fumed silica, ground silica, precipitated silica, and the like. Silica-based fillers are able to provide a thixotropic property to the compositions, resulting in sheer thinning when agitated (such as when dispensed through a needle or agitated after being placed) and then thickening when agitation ceases, thereby resulting in a composition that becomes more viscous. This provides improved application control of the acidic compositions when applied using an applicator device such as the dento-infusor device as compared to non-viscous compositions it helps to keep the composition in place where applied.
Examples of other useful inorganic fillers include metal oxides such as aluminum oxide and titanium dioxide.
When an inorganic filler is included in the composition according to the invention, they are preferably included in an amount in a range from about 0.1% to about 30% by weight of the composition, more preferably in a range of about 0.1% to about 10% by weight.
E. Other Additives
The inventive compositions may also include other adjuvents and active ingredients such as flavorants, desensitizing agents (e.g., KNO3), anticariogenic agents (e.g., fluoride compounds), antimicrobial agents (e.g., antibiotics), stabilizing agents (e.g., EDTA), and the like. The carrier is preferably substantially free of abrasives.